In the food industry, these active substances may be more particularly polysaccharides or oligosaccharides of the dextrin, maltodextrin, polydextrose or fructo-oligosaccharide type, but also polyols, for instance sorbitol, xylitol, mannitol, lactitol, maltitol, erythritol and isomalt.
It is known practice to use these active substances as such, and also as fillers for other active substances such as strong sweeteners, prepared by chemical synthesis, of the saccharin, aspartame, acesulfame K, cyclamate, stevioside, sucralose, neotame or alitame type.
In the pharmaceutical industry, it may be desirable to use these fillers in combination with, for example, pharmaceutical active principles such as antipyretic analgesics, in particular aspirin and its derivatives, paraminophenol derivatives (such as paracetamol) or pyrazolone derivatives.
Granulation procedures are often used to take full advantage of the powdered form of these active substances or these mixtures of active substances since it is often desirable to increase their particle size for technical and economic purposes.
The two main reasons for this new formulation are:                firstly essentially commercial, given that a granule provides a better appearance and is easier for the user to handle,        secondly strictly technical, because a granule slots more readily into a rational production process, in terms of being more readily conveyed, of better flow, of lack of formation of dust, of better homogeneity in a mixture with other substances, etc.        
However, it is extremely rare to be able to risk direct tableting of an active substance or a mixture of active substances, especially if they are effective at very low doses.
It is therefore necessary to formulate these compounds with excipients such as adjuvants (also called granulation binders) in order to confer on the final tablet both mechanical and functional qualities.
Two techniques are normally used to obtain a granule: the wet granulation technique and the dry granulation technique.
In the case of the wet granulation technique, the product to be granulated, that is either naturally wet because of its upstream production procedure, or artificially wetted with a solvent (water or organic solvent), is in a pasty form at the time of granulation.
Two methods are conventionally used for wet granulation: mechanical methods and physical methods.
The mechanical methods consist of grinding, rotor granulation or extrusion methods, well known to those skilled in the art.
Physical granulation methods that use more natural (and thus less aggressive) product granulation technology, by granulating the product either on itself or on an initiator, are however preferred.
The granulation generators per se are centrifugal force, centripetal force or universal gravity, combined with a granulation binder, conventionally consisting of water, of a solution of the product to be granulated, of alcohols or of a glaze, etc.
The product to be granulated is therefore moved around in a tank, for example by means of a pulsed airflow, or on a spherical disk or with a blade rotor (depending on the product and the effect to be obtained).
It continually receives a spray of granulation binders in liquid form to ensure agglomeration.
Thus this method makes it possible to prepare a homogeneous mixture by direct contact between the product to be granulated and the granulation binder. Intimate mixing of the two components is then facilitated.
A horizontal rotary knife can subsequently break up the clods of large agglomerates.
In this method, which is by far the one most preferred by those skilled in the art, it is however necessary for the granulation binder, once dissolved, to have a suitable viscosity, i.e.:                a sufficiently low viscosity to allow the solution containing the granulation binder to be readily pumped, in order to prevent clogging problems at the outlet of the injection nozzles, so as to promote the formation of fine droplets and to provide an even distribution thereof in the granulation tank,        a sufficiently high viscosity to allow the compound to play its role of granulation binder.        
The dry granulation technique consists of an operation referred to as “compacting” of the powder to be granulated, thus allowing such procedure to be carried out in simple turbines, or compacters, or in reactors under vacuum.
Use is made of methods of the “sintering” type, which bring about superficial fusion of the particles in contact, thus resulting in granulation by agglomeration.
Use is also made of techniques referred to as “agglomeration by hybridization”, which consist in combining only mechanically two distinct particles of different size, in general in a ratio of 1 to 10, in such a way that the small particles either become embedded discontinuously at the surface of the large particle or constitute a continuous film encompassing the entire sphere.
This technology is preferred when granules of thermosensitive active principles must be prepared, since it is known that this method generates only minimal heating, while at the same time promoting mechano-chemical reactions that make it possible to provide good cohesion of the granules.
The granulation binders, depending on their initial particle size, can play this role of large particles that make it possible to attach active substances conventionally having a finer particle size.
Direct association between particles of substances to be granulated and of granulation binders is then promoted.
The drawback of the dry granulation technique is that the subsequent sizing step generates a considerable production of fines.
The wet granulation technique has the advantage of producing no fines or, if it does produce them, doing so in smaller proportions.
However, the choice of using one or the other approach depends especially on the nature of the active substance to be granulated and, most particularly, on its behavior during the granulation operations.
Subsequently, the definitions of the granulation approach and of the granulation binder for granulating said active substance make it possible to adapt the physical and mechanical qualities of the granule obtained, i.e. its mean diameter, its density, its flow capacity, its residual water content and its friability.
Initial studies were interested in the granulation binder qualities that some active substances might themselves have, and thus do not require the addition of exogenous granulation binders that might alter the quality of said active substance to be granulated (such as the glazes or alcohols mentioned above).
Granulation of the active substance is carried out using a diluted solution of this same active substance as a granulation binder.
For example, Velasco et al., in Drug Development and Industrial Pharmacy, 21 (10), 1235-1243, 1995, described the flow properties of maltodextrin powders that could be used as a direct tableting vector.
According to them, the flow parameter of the starting powder is in fact of critical importance for its formulation.
Some maltodextrins, as long as they have satisfactory flow properties, can thus be advantageously used for granulating other compounds, such as active principles of pharmaceutical interest.
Velasco et al. have measured the bulk density, compressibility, dynamic angle of repose and especially flow capacity parameters of four maltodextrin powders available from the company Grain Processing Corp.
Velasco et al. have especially shown that these maltodextrins have completely different flow capacities, depending on the “friction index” parameter of the powder of the maltodextrins under consideration.
Some maltodextrins are entirely satisfactory, whereas others, such as Maltrin® M 150, do not even pass through the orifice of the device for measuring the flow capacity.
This great behavioral heterogeneity of said maltodextrins does not therefore promote their unconditional use in granulation, and therefore only partially facilitates their selection as granulation binders.
The other active substances, such as sugars, polyols, strong sweeteners or enzymes, do not have any particular capacities for granulation.
Xylitol or mannitol crystals for example show no capacity for direct tableting, neither do strong sweeteners such as aspartame.
For these particular active substances, an exogenous granulation binder is therefore essential for their formulation as granules.
U.S. Pat. No. 5,583,351 describes a method for preparing a dense product based on aspartame in powdered form, which does not have the drawbacks of the starting sweetener, i.e. its poor solubility in water, its tendency to form dust or its strong hygroscopicity.
It does not involve granulating the aspartame as it is, but granulating the aspartame, by centrifugation, extrusion, spheronization or atomization techniques, with a binder consisting of maltodextrins, of dextrins, of gum arabic, of polyol, of polydextrose or of soluble starch.
However, it is necessary to introduce up to 40% of this granulation binder. Where maltodextrins are chosen as granulation binders, mixtures must contain from 15 to 25% by weight thereof.
Another drawback of these granulation binders is that they do not provide the active substance to be granulated with any nutritional plus-value.
It has therefore been recommended to produce granules of these active substances by incorporating dietary fiber into them.
The dietary fiber effects of several soluble starch derivatives have therefore been developed. These fiber effects are the result of both the combination of hydrolysis reactions and transglucosylation reactions which confer on said starch derivatives properties identical to those of dietary fiber (in Englyst and Cummings, American Journal of Clinical Nutrition, 1997, 45, pp. 423-431).
Thus, patent application JP No. 2000-37 169, discloses strong sweetener preparations (aspartame, saccharin, sucralose, neotame and derivatives thereof) that have a low energy value, that are not very viscous and that have physiological functions.
These novel low-calorie aspartame preparations are aspartame containing-granules with at least 30% by weight, or even at least 50% by weight, of dietary fiber, which are provided by indigestible dextrins.
The granulation procedure described in patent JP No. 2000-37 169 consist either in atomizing a mixed aqueous solution of an indigestible dextrin and of a strong sweetener or in creating a core of indigestible dextrins onto which said strong sweetener is sprayed.
However, in these two procedures, the indigestible dextrins must be introduced at high concentration. It is even recommended to introduce said indigestible dextrins in proportions reaching virtually the entire mixture.
It is in fact acknowledged that these strong sweeteners are active substances that are effective at low dose, given their sweetening power being up to 130 to 8000 times greater than that of sucrose.
These indigestible dextrins are therefore used as a carrier for active substances, and not as granulation binders. Consequently, they are only intended for granulation of active substances that are effective in very small amounts.
Patent application US 2002/0146.487 describes the coating of soybean proteins with a thin layer of indigestible carbohydrates, followed by a granulation step with lecithin.
However, the aim of this method is the production of readily dispersible soybean protein granules.
As a matter of fact, Soybean proteins already have excellent granulation capacities (cf. tofu, which is an agglomerated soybean protein).
The coating method is carried out in such a way as to prevent penetration of the carbohydrates into the protein agglomerate. The lecithin is chosen for its surfactant properties used conventionally for promoting protein dispersibility.
None of these two components is used in the patent application as a granulation binder, quite the contrary.
In view of the foregoing, it appears that there is no simple granulation method using a granulation binder that to provide a solution to the technological constraints of preparing granules of active substances in terms of mechanical stability (flow capacity, friability, rapid dissolution in water, compressibility) and to confer, on the resulting granules, additional nutritional properties (for example dietary fiber effects), without necessarily using large amounts of said granulation binder.
To the applicant company's credit, it has succeeded in reconciling these objectives, that are difficult to reconcile, by imaging and developing, at the expense of considerable research, a simple method for preparing granules of active substances containing dietary fiber.